title: Targeted urine microscopy in Anderson-Fabry disease: a cheap, sensitive and specific diagnostic technique.
abstract: BACKGROUND
  Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder resulting from the deficiency of trihexosylceramide α-galactosidase (α-Gal A). The diagnosis is often missed or delayed, and specific diagnostic tests (serum α-Gal A activity, genotyping or biopsy) are expensive and not widely available. We evaluated the diagnostic potential of urine microscopy in AFD.
  
  
  METHODS
  We studied 35 male and female AFD patients across a wide phenotypic spectrum and 21 controls with other renal diseases. Fresh urine sediment was examined under phase-contrast microscopy using polarized light for Maltese cross (MC) particles, anti-CD77 antibody to detect globotriaosylceramide (GL3, the substrate of α-Gal A), and anti-podocalyxin antibody to assess podocyte excretion.
  
  
  RESULTS
  Characteristic MC 2 particles and anti-CD77 binding within vacuolated urinary epithelial cells were both detected in AFD with high sensitivity and specificity (MC 2 detection sensitivity 100%, 95% confidence interval (CI) 85.4-100%, specificity 100%, CI 80.8-100%; anti-CD77-binding sensitivity 97.1%, CI 83.3-99.9, specificity 100%, CI 80.8-100%). Albuminuria (urinary albumin-to-creatinine ratio, ACR) correlated with quantitative particle excretion--in low, intermediate and high MC excretors, and median ACR was 1.6, 6.9 and 20.0 mg/μmol, respectively (analysis of variance P = 0.017). Podocyte staining was positive in ~50% of all AFD patients and was similar in those with and without clinical Fabry nephropathy (FN), whether or not treated with enzyme replacement.
  
  
  CONCLUSIONS
  Targeted urinary microscopy is a non-invasive, inexpensive, accessible and rapid diagnostic technique, especially applicable where serum α-Gal A activity and genotyping are not affordable or available. As the number of urinary MC 2 particles increases with rising albuminuria, the technique may also be useful in assessing FN burden.
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Parkville, Melbourne, Australia.
authors.forename: Mathu
authors.initials: M
authors.lastname: Selvarajah
authors.forename: Kathy
authors.initials: K
authors.lastname: Nicholls
authors.forename: Tim D
authors.initials: TD
authors.lastname: Hewitson
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Becker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003581:Cytodiagnosis; D004847:Epithelial Cells / Q000473:pathology*; D000795:Fabry Disease / Q000175:diagnosis* / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008858:Microscopy, Phase-Contrast; D008875:Middle Aged; D012680:Sensitivity and Specificity; D014281:Trihexosylceramides / Q000652:urine*; D016482:Urinalysis; D055815:Young Adult; D000519:alpha-Galactosidase / Q000378:metabolism
chemical_list: D014281:Trihexosylceramides; C018549:globotriaosylceramide; C027256:trihexosylceramide alpha-galactosidase; D000519:alpha-Galactosidase